Reactivity of 6-phosphogluconolactone with hydroxylamine: The possible involvement of glucose-6-phosphate dehydrogenase in endogenous glycation reactions

Rakitzis, Emmanuel T.; Papandreou, Photini

doi:10.1016/s0009-2797(98)00026-x

Cited by 41 publications

(43 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Loss of the activity of DevB is likely to have much more impact on flux through the PPP than mutations in any one of the zwf genes have, because DevB is the only protein known to be catalytically involved in hydrolysis of 6-phosphogluconolactone (23). The results also suggest that there are no significant adverse effects produced by potential accumulation of the toxic compound 6-phosphogluconolactone (33) in the organism under the conditions examined. Although the lactone can undergo spontaneous hydrolysis, the low rate of this reaction would still be likely to cause a significant reduction in flux through the PPP.…”

mentioning

confidence: 80%

Engineering of Primary Carbon Metabolism for Improved Antibiotic Production in Streptomyces lividans

Butler

Bruheim

Jovetic³

et al. 2002

Appl Environ Microbiol

View full text Add to dashboard Cite

Deletions were made in Streptomyces lividans in either of two genes (zwf1 and zwf2) encoding isozymes of glucose-6-phosphate dehydrogenase, the first enzyme in the oxidative pentose phosphate pathway (PPP). Each mutation reduced the level of Zwf activity to approximately one-half that observed in the wild-type strain. When the mutants were transformed with multicopy plasmids carrying the pathway-specific transcriptional activator genes for either the actinorhodin (ACT) or undecylprodigiosin (RED) biosynthetic pathway, they produced higher levels of antibiotic than the corresponding wild-type control strains. The presumed lower flux of carbon through the PPP in each of the ⌬zwf mutants may allow more efficient glucose utilization via glycolysis, resulting in higher levels of antibiotic production. This appears to occur without lowering the concentration of NADPH (the major biochemical product of the oxidative PPP activity) to a level that would limit antibiotic biosynthesis. Consistent with this hypothesis, deletion of the gene (devB) encoding the enzyme that catalyzes the next step in the oxidative PPP (6-phosphogluconolactonase) also resulted in increased antibiotic production. However, deletion of both zwf genes from the devB mutant resulted in reduced levels of ACT and RED production, suggesting that some of the NADPH made by the PPP is utilized, directly or indirectly, for antibiotic biosynthesis. Although applied here to the model antibiotics ACT and RED, such mutations may prove to be useful for improving the yield of commercially important secondary metabolites.

show abstract

mentioning

confidence: 80%

Engineering of Primary Carbon Metabolism for Improved Antibiotic Production in Streptomyces lividans

Butler

Bruheim

Jovetic³

et al. 2002

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…human erythrocytes, the activity levels of the PGL enzyme are several times higher than those of glucose-6-phosphate dehydrogenase (18). It has been proposed that the role of the PGL enzyme in vivo is rapid and effective hydrolysis of lactones, preventing ester-and amide-forming reactions involving, e.g., basic amino acids, such as arginine and lysine (6).…”

Section: Figmentioning

confidence: 99%

Suppressing Posttranslational Gluconoylation of Heterologous Proteins by Metabolic Engineering of Escherichia coli

Aon¹,

Caimi²,

Taylor³

et al. 2008

Appl Environ Microbiol

View full text Add to dashboard Cite

Minimization of chemical modifications during the production of proteins for pharmaceutical and medical applications is of fundamental and practical importance. The gluconoylation of heterologously expressed protein which is observed in Escherichia coli BL21(DE3) constitutes one such undesired posttranslational modification. We postulated that formation of gluconoylated/phosphogluconoylated products of heterologous proteins is caused by the accumulation of 6-phosphogluconolactone due to the absence of phosphogluconolactonase (PGL) in the pentose phosphate pathway. The results obtained demonstrate that overexpression of a heterologous PGL in BL21(DE3) suppresses the formation of the gluconoylated adducts in the therapeutic proteins studied. When this E. coli strain was grown in high-cell-density fed-batch cultures with an extra copy of the pgl gene, we found that the biomass yield and specific productivity of a heterologous 18-kDa protein increased simultaneously by 50 and 60%, respectively. The higher level of PGL expression allowed E. coli strain BL21(DE3) to satisfy the extra demand for precursors, as well as the energy requirements, in order to replicate plasmid DNA and express heterologous genes, as metabolic flux analysis showed by the higher precursor and NADPH fluxes through the oxidative branch of the pentose phosphate shunt. This work shows that E. coli strain BL21(DE3) can be used as a host to produce three different proteins, a heterodimer of liver X receptors, elongin C, and an 18-kDa protein. This is the first report describing a novel and general strategy for suppressing this nonenzymatic modification by metabolic pathway engineering.

show abstract

“…Lactone Reactivity Toward Nucleophile Compound-The 6-P-G-L reactivity toward a nucleophile model compound, hydroxylamine, was assayed at 5°C and a pH of 6.7 by measuring its conversion into hydroxamate (6). Rate constant values were estimated by fitting the increase in hydroxamate concentration and the ␥(t) curves upon the addition of 25 mM hydroxylamine.…”

Section: Figmentioning

confidence: 99%

“…Our results confirm that human and Trypanosoma brucei 6PGLs are highly active enzymes and highlight their important role in the cell. Particularly, they seem to prevent the accumulation of 6-P-G-Ls that were described previously as highly electrophilic compounds capable of affecting the integrity of endogenous cell compounds (6). This hypothesis is assessed by this investigation, and both 6-P-G-L forms (␦ and ␥) are compared with respect to their reactivity.…”

mentioning

confidence: 92%

NMR Spectroscopic Analysis of the First Two Steps of the Pentose-Phosphate Pathway Elucidates the Role of 6-Phosphogluconolactonase

Miclet¹,

Stoven²,

Michels³

et al. 2001

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

The pentose-phosphate pathway provides reductive power and nucleotide precursors to the cell through oxidative and nonoxidative branches, respectively. 6-Phosphogluconolactonase is the second enzyme of the oxidative branch and catalyzes the hydrolysis of 6-phosphogluconolactones, the products of glucose 6-phosphate oxidation by glucose-6-phosphate dehydrogenase. The role of 6-phosphogluconolactonase was still questionable, because 6-phosphogluconolactones were believed to undergo rapid spontaneous hydrolysis. In this work, nuclear magnetic resonance spectroscopy was used to characterize the chemical scheme and kinetic features of the oxidative branch. We show that 6-phosphogluconolactones have in fact a nonnegligible lifetime and are highly electrophilic compounds. The ␦ form (1-5) of the lactone is the only product of glucose 6-phosphate oxidation. Subsequently, it leads to the ␥ form (1-4) by intramolecular rearrangement. However, only the ␦ form undergoes spontaneous hydrolysis, the ␥ form being a "dead end" of this branch. The ␦ form is the only substrate for 6-phosphogluconolactonase. Therefore, 6-phosphogluconolactonase activity accelerates hydrolysis of the ␦ form, thus preventing its conversion into the ␥ form. Furthermore, 6-phosphogluconolactonase guards against the accumulation of ␦-6-phosphogluconolactone, which may be toxic through its reaction with endogenous cellular nucleophiles. Finally, the difference between activity of human, Trypanosoma brucei, and Plasmodium falciparum 6-phosphogluconolactonases is reported and discussed.

show abstract

Reactivity of 6-phosphogluconolactone with hydroxylamine: The possible involvement of glucose-6-phosphate dehydrogenase in endogenous glycation reactions

Cited by 41 publications

References 38 publications

Engineering of Primary Carbon Metabolism for Improved Antibiotic Production in Streptomyces lividans

Engineering of Primary Carbon Metabolism for Improved Antibiotic Production in Streptomyces lividans

Suppressing Posttranslational Gluconoylation of Heterologous Proteins by Metabolic Engineering of Escherichia coli

NMR Spectroscopic Analysis of the First Two Steps of the Pentose-Phosphate Pathway Elucidates the Role of 6-Phosphogluconolactonase

Contact Info

Product

Resources

About